Q&A: A healthy chat with the Center for Global Development’s health policy leader

nm1211-1534-I1.jpgSince its launch in 2001, the Center for Global Development (CGD) has been instrumental in convening working groups and issuing reports that shape the agenda for a range of topics that affect global poverty and people of the developing world. At the helm of its global health effort is Amanda Glassman. As the daughter of US Foreign Service diplomats, Glassman was exposed to disparities in public health in developing countries from a very young age. So it was a no-brainer for Glassman that she would devote her career to tackling those inequalities. She has spent the last two decades at places like the US Agency for International Development, the Inter-American Development Bank and the Brookings Institution. Last year, she joined CGD as the director of its global health policy division.

One idea that the $10-million-a-year, Washington, DC–based think tank has championed with some success is what’s known as an advance market commitment (AMC), a financial instrument that incentivizes vaccine development for diseases primarily affecting low-income countries. It’s for this influence that the center, which is mainly funded by governments and philanthropic entities, was ranked the fifteenth most important US think tank by Foreign Policy magazine in 2008. In recognition of CGD’s ten-year anniversary last month, Elie Dolgin spoke to Glassman about how the think tank turns its words into actions.

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Four-in-one HIV pill may be exception among combination drugs

By Hannah Waters

jetsons-peek-a-boo-prober.jpgThe 1960s cartoon The Jetsons envisioned a future where single pills provided the same nutrition, taste and satiation as food that required chewing. That time-saving tablet remains a pipe dream, but the drugmaker Gilead is trying to deliver a similarly inspired pill for HIV medicines. On 27 October, the California company submitted an application to the US Food and Drug Administration (FDA) for its four-in-one HIV pill, which, if approved, would contain more medicines than any pill currently on the US market. The so-called ‘Quad’ pill promises the same virus-controlling ability as the four drugs separately but should be easier to use for people with the infection.

The idea of combining multiple medicines is seen by some as an easy shortcut to reinvigorating old products. Drugmakers can often simply repackage what’s already on the market, and, because the individual components have already been approved, the hassle of large clinical trials is off the table. The FDA generally requires only simple bioequivalence tests to ensure that drug dosing is consistent with the individual medicines, and, at most, a small human trial to prove similar efficacy.

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New HCV drugs trigger race for more tolerable therapies

By Sarah C P Williams

The approval this year of the first direct-acting antiviral drugs for the hepatitis C virus has ushered in a new era of treatment. Since the mid-May launch of Incivek (telaprevir) and Victrelis (boceprevir) — both of which disrupt viral replication by inhibiting HCV’s protease protein — physicians have rapidly been prescribing the pills to many of the estimated 180 million people worldwide who are infected with HCV. This is reflected in October earnings reports showing that sales of Incivek reached nearly $420 million in the third quarter of this year alone, which puts it on pace to become the fastest blockbuster in the history of the pharmaceutical industry.

But Incivek, from Vertex Pharmaceuticals of Cambridge, Massachusetts, and Victrelis, from Merck of Whitehouse Station, New Jersey, currently have a catch. Each medicine must be taken with a broad-acting antiviral pill called ribavirin as well as with regular injections of pegylated interferon. Historically, viral clearance occurs in around half of all people who take interferon together with ribavirin, but another 20% can be cured of their HCV when doctors throw one of the new polymerase inhibitors into the mix. Interferon stimulates the immune system but comes with side effects ranging from flu-like fatigue to severe depression to cardiac arrhythmias. Up to a third of people on the protein ultimately stop the therapy early because of adverse reactions.

Against this backdrop, there was much fanfare over the 1 November announcement by the Princeton, New Jersey–based company Pharmasset that it would initiate the world’s first phase 3 clinical study involving an all-oral, interferon-free protocol before the end of the year. The 500-person trial will compare a three-month regimen of the company’s experimental polymerase inhibitor, PSI-7977, together with ribavirin against a six-month course of interferon plus ribavirin. PSI-7977 works by becoming incorporated into RNA chains being made by HCV, stopping the virus from replicating.

“There’s been real concern that we might never be able to get away from interferon entirely, but now we’re starting to get an inkling that that might not be the case,” says Gary Davis, director of the general and transplant hepatology unit at the Baylor University Medical Center in Dallas.

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A retrospective of retractions: the striking record in 2011

John Darsee was a young clinical investigator with a long list of publications in top-tier journals and a promising career ahead of him in cardiology research. Described by a former supervisor as “one of the most remarkable young men in American medicine,” Darsee was offered a faculty position at the Harvard Medical School in Boston at the age of 33. But then his career quickly started to unravel. One day, colleagues caught Darsee fraudulently labeling data for a study into heart attacks; further investigations revealed scientific misconduct on a massive scale, and, eventually, Darsee was fired and barred from receiving federal grant money for ten years. More than 80 of his papers were withdrawn from the literature. He ultimately apologized for publishing “inaccuracies and falsehoods.”

That was twenty years ago. But the problem of retractions has not gone away — in fact, it may be getting worse, with the number of such notices on the rise. And whereas the Darsee case took more than decade to come to light (and only then because of an accidental discovery), these days image detection software and the vigilance of media outlets such as Retraction Watch (see ‘The Yearbook’) can catch irregularities — be they due to innocent error or misconduct — much sooner. The ability to track these changes provides benefits to biomedicine, as experiments in the scientific literature lay the foundation for future experiments. Here we look back at instances from the past year where multiple papers from certain investigators came under scrutiny.

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EDITORIAL: Reaction to retractions

homecoverDEC11.gifRetracting a paper is perhaps the most unpleasant task a journal has to face, particularly if the retraction involves scientific misconduct. With the number of retractions on the rise, an improved mechanism to deal with misconduct is necessary.

Click here to read the editorial from the December 2011 issue of Nature Medicine.

Study challenges genetic conventions in personalized medicine

Drugs

A more refined genomic approach to personalized medicine could make drugs such as statins safer for patients, the authors of a new paper recommend.

Hospitals increasingly use genetic testing to determine whether people are at risk for developing toxic levels of certain drugs in their bloodstreams due to common genetic variants that cause slower clearance of medication by the liver. A study published today in Genome Research strengthens the case for health providers to incorporate tests for rare variants that also influence how the body clears medications from the blood.

The study focused on the medication methotrexate, used to treat acute lymphoblastic leukemia as well as autoimmune disorders such as rheumatoid arthritis. (The drug is sold as Trexall, Rheumatrex by Teva Pharmaceutical Industries and DAVA Pharmaceuticals, respectively.) The SLCO1B1 gene encodes a transporter in the liver that is important for clearing the drug from the body.

Scientists already know that about 10% of the population possesses a common variant of the SLCO1B1 gene that causes methotrexate to be cleared from the body more slowly. As a result, doctors personalize the dosage of methotrexate based on common gene variants to avoid increased side-effects in those patients with low drug clearance. The side–effects of methotrexate are far from trivial — a build-up of medication in the blood can lead to mouth and intestinal sores and kidney failure.

However, in the report published today researchers report that in an additional 2% of people with low clearance, rare gene variants in SLCO1B1 are to blame.

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Bone marrow donors can be paid, US court rules

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In a ruling that may bring relief to cancer patients across the US, a federal appeals court said that a decades-old law banning the sale of human organs does not apply to bone marrow donations.

The US National Organ Transplant Act of 1984 prohibits financial compensation for human organ donations, including bone marrow, but allows people to be paid for blood and plasma donations. At the time, lawmakers made that distinction because the method used to extract marrow was dangerous, and monetary kickbacks could have encouraged desperate people to take unnecessary risks. As a disincentive to sell organs, the crime was made punishable by up to five years in prison. But a group of cancer victims, parents of sick children, a physician and a Californian non-profit called MoreMarrowDonors.org challenged the status quo, arguing that reimbursement was essential to plug the country’s shortage of bone marrow donors.

In a decision released yesterday, the US Court of Appeals for the Ninth Circuit, which covers much of the western part of the country, agreed. “The court’s decision will fundamentally change treatment options for people with deadly blood diseases,” Jeff Rowes, the attorney from the Institute for Justice in Arlington, Virginia who argued the case, told Nature Medicine.

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A dance with death: Alvin Ailey premieres hip-hop ballet inspired by AIDS

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Dance companies and drugmakers are strange bedfellows. For the most part, leotard-wearing dancers and lab-coated scientists remain firmly footed in different professional spheres. But at 8pm last night, the curtain went up on a unique collaboration. In honor of World AIDS Day, New York-based Bristol-Myers Squibb (BMS) and the Alvin Ailey American Dance Theatre partnered to produce an original dance performance inspired by the stories of people living with HIV.

The New York City Center in Manhattan was sold out and buzzing with excitement for the opening. In the audience for the show’s premiere were the ten people whose stories inspired the new work, called Home. They are the winners of BMS’s ‘Fight HIV Your Way’ contest, which invited HIV-positive people to submit photographs and essays that embodied their personal experience with the life-threatening virus.

For this year’s competition — the third installment of the contest and the largest yet, with more than 1,300 submissions — BMS decided to bring the ten winning entries to life through the medium of live dance. The winners included a photo of Jack Miller of Perth Amboy, New Jersey, in zombie make-up, intended to show the ‘walking dead’ nature of people living with HIV/AIDS, and another by Kurt Weston of Huntington Beach, California, with him staring into the camera holding a heart next to his chest. Weston lost his sight to cytomegalovirus retinitis, a common problem for people with HIV/AIDS. In his entry, he explained that still has the love and commitment of his partner.

“The images were so powerful,” Judith Jamison, Ailey’s former artistic director and a judge for this year’s contest, told Nature Medicine. “I was going over every entry three or four times at first just taking it in.”

It’s an unorthodox pharma promotion, to be sure. BMS is the maker of Reyataz, a once-daily HIV protease inhibitor drug that is featured prominently on the contest’s website and in the dance performance brochure.

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UNAIDS-backed reports sing the same tune but stay silent on funding crunch

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Today is World AIDS Day, and in the run-up to the date this year, UN agencies published two reports on the state of the HIV epidemic. For the most part, the good news from these reports has captured the headlines: Topping the list of heartening statistics, 47% of people in low and middle-income countries now have access to anti-retroviral treatment (ART), up 9% from the number covered in 2009.

But a few cracks lie beneath the positive numbers. In the past week, The Economist chided the UN for publishing the two reports, one on 21 November from the Joint United Nations Programme on HIV/AIDS (UNAIDS) and another on 30 November in partnership with the World Health Organization (WHO), and UNICEF, when these UNAIDS-backed agencies could have just as well consolidated the information in a single analysis with a unified message. Conspicuously missing from the documents is the lack of a cohesive vision for meeting funding needs in a tough global economy, and that is disconcerting.

The economic reality hit home for UNAIDS when their largest funding partner, the Global Fund to fight AIDS, TB, and Malaria, canceled its next fundraiser because it had failed to collect the $13 billion it needs to fund its programs. Meanwhile, the President’s Emergency Plan for AIDS Relief (PEPFAR) has also decreased its treatment funding for antiretrovirals by $170 million since 2008

The international funding community “is kicking out the last leg of the stool,” says Sharonann Lynch, a New York-based HIV policy advisor for Doctors Without Borders (MSF). “There is this good news from the UN, but the whole thing is going to collapse without funding.”

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